Since HMGCoA reductase is the major site of the control of cholesterol biosynthesis, it is proposed to investigate the mechanism of the effect of a variety of physiological states on HMGCoA reductase activity, e.g. fasting, cholesterol feeding, supplementation with hormones, interruption of the enterohepatic circulation of bile. The synthesis and the degradation of the enzyme protein as well as possible allosteric effects will be studied in liver, and intestinal mucosal cells by means of immunochemical techniques which will enable the enzyme protein to be extracted from crude cell homogenates relatively easily. The mechanism of inhibition of the enzyme activity by cholesterol derivatives, e.g. 7-ketocholesterol and 25-hydroxycholesterol will be investigated by the same mechanism. The mechanism of feedback regulation of cholesterol synthesis by various lipoprotein fractions in intestinal mucosal cell, various fibroblast cell lines arterial smooth muscle cells will also be examined. BIBLIOGRAPHIC REFERENCE: The Inhibitory Effect of ATP on HMGCoA Reductase by Jacob C. Chow, Malcolm J.P. Higgins and Harry Rudney (1975) Biochem. Biophys. Res. Comm. 63, 1077.